BACKGROUND Because of the small number of cases (five) reported between 1929 and 1969 and a significant increase reported in the decade of the 1970s, the Familial Ovarian Cancer Registry was established in 1981 to study the occurrence of familial ovarian cancer in the United States. METHODS Any woman (with or without ovarian cancer herself) who contacted the Registry and demonstrated a familial history of ovarian cancer was added to the Registry as an index case. RESULTS From 1981 through May 31, 1991, 658 families for a total of 1568 cases of familial ovarian cancer were accessioned into the Registry. Of the 219 mothers and 251 daughters with familial ovarian cancer, the mean (58.5 years) and median (57.0 years) age at diagnosis of the mothers was significantly older than the mean (49.8 years) and median (49.0 years) ages of their daughters with ovarian cancer. Significantly more index cases without ovarian cancer had used oral contraceptives as compared to index cases with ovarian cancer (P < 0.001). Significantly more index cases with ovarian cancer used other estrogens as compared to index cases without ovarian cancer (P < 0.001). The Registry cases exhibited a higher proportion of serous adenocarcinoma, poorly differentiated adenocarcinoma, borderline carcinoma, and gonadoblastoma as compared to the 1978 SEER data. Mother and a minimum of one daughter was the most common relationship and was represented in 49.5% of the families with familial ovarian cancer. Sister-sister relationships were the second most frequent and accounted for 38.5% of the 658 families. CONCLUSIONS Familial ovarian cancer occurs most frequently in mother-daughter relationships followed by sister-sister and appears to be an autosomal dominant inheritance with variable penetrance.