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 measures 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.