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9515 Background: Alkylating agents are associated with a risk of male gonadal damage, even in patients treated during childhood. The purpose of this work was to compare this risk after treatment by ifosfamide vs cyclophosphamide during childhood. Methods: Evaluation was based on basal FSH measurement known for its correlation with spermatogenesis. LH and testosterone were also measured in most of the patients. 159 males were evaluated after treatment of a soft tissue sarcoma (79), osteoasarcoma (39), ewing (10), lymphoma (28), other (3). 100 patients received ifosfamide as unique alkylating agent and the other 59 received cyclophosphamide as the other unique alkylating agent between 1973 and 2000. Median age at treatment was 11.2 years (0–18 yrs). Median interval after the end of the treatment was 10.7 years (4.1–20.2 yrs), median age at evaluation was 21.4 years (17.5–36.1 yrs). Median dose of ifosfamide was 54 g/m2 (18- 114), median dose of cyclo was 8.3 g/m2 (4.6–22). Age at treatment and at evaluation were similar in both groups. Results: All males but two (17.5 and 26.5 yrs) had normal testosterone levels. LH was elevated in 14% of the patients. FSH was above laboratory upper limit in 28 of the 59 males (47.5%) treated with cyclophosphamide and was within the normal range in 94 of 100 patients (94%) treated with ifosfamide. Eight patients treated with cyclophosphamide fathered children. The median dose of cyclo was 5.6 g/m2 (4.8 - 10.8 g/m2). Six patients who received 51 to 54 g/m2 fathered children. The risk of abnormal FSH increased with the cumulative dose of cyclophosphamide: only 2/16 boys (12%) who received more than 12 g/m2 had a normal dosage of FSH, while 29/43 (67%) of the boys who received lower doses of cyclo did so. Conclusions: These results show a low risk of gonadal dysfunction in men exposed to ifosfamide (median dose 54 g/m2) compared to the results for males treated with cyclophosphamide. The risk of abnormal FSH increased with the cumulative dose of cyclophosphamide. No significant financial relationships to disclose.