Perinatal alloimmune thrombocytopenia (PAITP) causes intracranial haemorrhage in the fetus and neonate. However, the severity of the thrombocytopenia correlates poorly with maternal anti-platelet antibody titres. To test the hypothesis that reduced platelet production contributes to fetal thrombocytopenia in PAITP, maternal sera from three HPA-1a-negative mothers whose pregnancies were complicated by anti-HPA-1a (two severe cases, one mild case) were added to colony forming unit-megakaryocyte (CFU-MK) cultures from HPA-1a positive and negative individuals. Sera from the two severely affected pregnancies containing anti-HPA-1a caused 66-100% inhibition of HPA-1a-positive fetal and neonatal CFU-MK, whereas CFU-MK from two HPA-1a-negative mothers were not inhibited by the anti-HPA-1a-containing sera. Maternal serum from the case of mild PAITP caused only mild inhibition of HPA-1a-positive cord and adult CFU-MK and did not inhibit HPA-1a-positive fetal CFU-MK. Taken together, these findings suggest that reduced megakaryocyte production contributes to fetal thrombocytopenia due to maternal anti-HPA-1a antibodies and also that the degree of CFU-MK inhibition correlates with severity of fetal thrombocytopenia.