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Objective: To determine the likely factors that contribute to RhD sensitisation., Design: Retrospective study of all new cases of RhD sensitisation occurring between 1988 and 1991., Setting: Leeds Blood Centre, National Blood Service, Yorkshire., Population: One hundred and forty-seven cases of RhD sensitisation from 15 obstetric units within the Yorkshire region, of which 129 (312 pregnancies) could be assessed., Main Outcome Measure: S Identification of potential immunising events and adherence with recommendations on anti-D immunoglobulin administration., Results: Twenty-eight women (22%) had immune anti-D antibodies during their first pregnancy or at delivery and 50 (39%) in their second pregnancy. Overall, 98 potential immunising events were identified in 62 women, excluding delivery; 67 women (52%) had no events, other than delivery. Miscarriages and medical terminations of pregnancy accounted for 81% of all identified events. Iatrogenic failure to adhere to recommendations for the administration of anti-D immunoglobulin occurred in a significant proportion of women who subsequently developed immune anti-D antibodies. Anti-D immunoglobulin failed to protect against immunisation despite adherence to the protocol in 20 events (20%), 13 of which involved miscarriages or termination of pregnancy < 20 weeks of gestation. Potentially, antenatal prophylaxis might have prevented 86% of immunisations that were identified during the first pregnancy., Conclusions: The introduction of antenatal administration of anti-D immunoglobulin could significantly reduce the level of sensitisation in primigravidae, and adherence to recommendations for administration of anti-D immunoglobulin could be improved. Consideration should be given to reviewing the current recommendation that a dose of 250 IU of anti-D immunoglobulin is adequate following termination of pregnancy before a gestational age of 20 weeks.