No statistically significant deviations in phenotype frequencies of the 25 HL-A antigens or the ABO antigens were seen when 111 Caucasian patients with trophoblastic disease were compared with 1,259 healthy Caucasian controls. However, an increasein the incidence of HL-A11 was found in 39 patients who currently had the disease, but not in 72 who had recovered from the disease. Further, an increase in the frequency of W18 was observed among 18 patients who currently had 'invasive' disease (choriocarcinoma or invasive mole), but not in 44 who had recovered from such disease. If valid for larger patient population, these increases may suggest association of HL-A11 and W18 with the 'morbidity' of the trophoblastic disease. No increase in histocompatibility was seen in 45 patient-couples over 67 control-couples in terms of decrease in the number of male spouse's HL-A incompatibilities, and no significant difference was seen in the distribution of pregnancies in the two groups. No significant difference was observed in the incidence of different male-female combinations of ABO blood groups between 95 patient-couples and an equal number of control-couples. Lymphocytotoxic antibodies were found in 64 patients (158 sera) or 36% of the 178 patients (413 sera) examined. HL-A specific antibodies were found in 30 or 17% patients (39 sera). Of these 30, 24 patients had molar pregnancies and six had choriocarcinoma. Whether these antibodies have a role in the destruction of neoplastic tissue remains to be determined.