Development of the capacity for hepatic biotransformation of potentially toxic, endogenous compounds such as lithocholate may be dependent on induction by substrate or hormonal modulation. Our aim was to observe the ontogeny of hepatic sulfotransferase (ST) activity, a presumed detoxification pathway, and to determine the effect of substrate ingestion and cortisone administration on ST activity. Pregnant rats were fed a standard chow diet containing lithocholate; the maternal diet was continued during the suckling and weaning phase of the pups. Liver cytosol and serum were obtained from dams and from pups at weekly intervals from fetal life through 4 weeks of age. In controls, there was a progressive increase in hepatic ST activity from 6.2 +/- 2.9 pmol/mg protein per min, (mean +/- SEM) in fetal liver, 18.1 +/- 3.9 at 1 week, an 33.6 +/- 7.2 at 2 weeks to a peak of 56.4 +/- 11.8 at 3 weeks of age. In female rats older than 4 weeks of age, ST activity in hepatic cytosol was threefold higher than in males. There was a decline to adult levels (9.2 +/- 2.4 in males and 39.4 +/- 4.3 in females) at 56 days of life. Cortisone acetate administration had no effect on enzyme activity in pups except those 3 weeks old or older in which there was a precocious decrease in enzyme activity to adult levels. The administration of lithocholate caused a dose-related postnatal alteration of intrahepatic bile ducts manifest as cholangitis with ductular proliferation; hepatocytes were spared.(ABSTRACT TRUNCATED AT 250 WORDS)