Fecundability has been defined as the ability to achieve a recognized pregnancy. Several studies on caffeine and fecundability have been conducted but have been inconclusive. This may be explained partly by lack of stratification by smoking. Furthermore, few researchers have tried to separate the effect of caffeine from different sources (coffee, tea, cola, and chocolate). Clearly, the relationship between caffeine and fecundability needs further research, given the high prevalence of caffeine intake among women of childbearing age. We examined the independent and combined effects of smoking and caffeine intake from different sources on the probability of conception. From 1992 to 1995, a total of 430 couples were recruited after a nationwide mailing of a personal letter to 52,255 trade union members who were 20 to 35 years old, lived with a partner, and had no previous reproductive experience. At enrollment and in six cycles of follow-up, both partners filled out a questionnaire on different factors including smoking habits and their intake of coffee, tea, chocolate, cola beverages, and chocolate bars. In all, 1596 cycles and 423 couples were included in the analyses. The cycle-specific association between caffeine intake and fecundability was analyzed in a logistic regression model with the outcome at each cycle (pregnant or not pregnant) in a Cox discrete model calculating the fecundability odds-ratio (FR). Compared to nonsmoking women with caffeine intake less than 300 mg/d, nonsmoking women who consumed 300 to 700 mg/d caffeine had a FR of 0.88 [95% confidence interval (CI) 0.60-1.31], whereas women with a higher caffeine intake had a FR = 0.63 (95% CI 0.25-1.60) after adjusting for female body mass index and alcohol intake, diseases of the female reproductive organs, semen quality, and duration of menstrual cycle. No dose-response relationship was found among smokers. Among males, the same decline in point estimates of the FR was present. Smoking women whose only source of caffeine was coffee (300 mg/d) had a reduced fecundability odds-ratio (FR = 0.34; 95% CI 0.12-0.98). An interaction between caffeine and smoking is biologically plausible, and the lack of effect among smokers may be due to faster metabolism of caffeine. Our findings suggest that especially nonsmoking women who wish to achieve a pregnancy might benefit from a reduced caffeine intake.The independent and combined effects of smoking and caffeine intake from different sources on fecundability were assessed in a national survey of 423 Danish couples. Couples were recruited to the study in 1992-95 through a mailing to 52,255 female trade union members seeking women who were 20-35 years old, lived with a partner, had no previous pregnancies, and intended to discontinue contraception in order to become pregnant. A total of 1596 cycles were included in the 6-month study and the cycle-specific association between caffeine intake and fecundability was analyzed in a logistic regression model with the outcome (pregnant, not pregnant) in a Cox discrete model. Compared with nonsmoking women with a caffeine intake less than 300 mg/day, nonsmoking women who consumed 300-700 mg/day of caffeine had a fecundability odds ratio (FR) of 0.88 (95% confidence interval (CI), 0.60-1.31), while those with a higher consumption had an FR of 0.63 (95% CI, 0.25-1.60), after adjustments for body mass index, alcohol intake, diseases of the female reproductive organs, semen quality, and duration of the menstrual cycle. No such dose-response relationship was detected among smokers. The same decline in point estimates of the FR was present was males. Smoking women whose only source of caffeine was coffee (over 300 mg/day) had a reduced FR (0.34; 95% CI, 0.12-0.98). The lack of adverse effect among smokers may be due to faster metabolism and clearance of caffeine. Overall, these findings indicate that nonsmoking women who wish to achieve pregnancy should consider reducing their caffeine intake.