The role of contraceptive steroids in the etiology or pathogenesis of hepatocellular carcinoma in urban South African black women was investigated in a hospital-based case and control study. Participating were 46 women, 19 to 54 yr old, with carcinoma, and 92 matched controls. South African blacks have a high incidence of hepatocellular carcinoma, and urban black women have used contraceptive steroids fairly widely for a number of years. Use of contraceptive steroids for longer than 6 mo (mean duration 46.7 mo) was not found to pose a risk for development of hepatocellular carcinoma in this population--relative risk 0.8 (95% confidence interval [C.I.] 0.4 to 1.7). This was also true of use for longer than 8 yr--relative risk 0.6 (95% C.I. 0.2 to 2.5), and if a combination of an estrogen and a progestogen or a progestogen alone was used (relative risk 1.7 [95% C.I. 0.7 to 4.2] and 0.4 [95% C.I. 0.1 to 1.2], respectively). Chronic hepatitis B virus infection was confirmed to have an etiological association with hepatocellular carcinoma, but there was no evidence that contraceptive steroids acted as a co-carcinogen with the virus or, conversely, that they played a causal role in patients negative for hepatitis B surface antigenemia. We cannot, however, exclude the possibility that contraceptive steroids may play a causal role in hepatocellular carcinoma in black women who have never been infected with the hepatitis B virus. Nor was there evidence that contraceptive steroids acted in concert with either cigarette smoking or chronic alcohol abuse in hepatocarcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)