Concentrations of neutral organic contaminants and activities of microsomal P-450 mixed-function oxidase (MFO) were measured in the livers of the starry flounder Platichthys stellatus (Pallas), collected from more- and less-contaminated sites in San Francisco Bay, during the 1984–1985 reproductive season. Starry flounder collected at the Berkeley (Bk) site, located in the more urbanized central portion of San Francisco Bay, had greater liver concentrations of polychlorinated biphenyls (PCBs) and polynuclear aromatic hydrocarbons (PAH) (fluorescence equivalents of pyrene) than those collected at a site in northern San Pablo Bay (SP), where urban development is less intense and more distant. Hepatic aryl hydrocarbon hydroxylase (AHH) activity, a particular MFO, in males and in gonadally immature females fluctuated significantly from September 1984 through April 1985 with the Bk population exhibiting significantly greater activities during this period. Site differences were especially notable during the time of spawning (January–March), as AHH activities of starry flounder from SP declined and those from Bk remained elevated. These site differences appear to be due to P-450 isozymes (e.g. P-450E) whose activities are inducible by some PCBs and PAHs, as males and gonadally immature females from the two sites were not different in their hepatic AHH activities when assayed in the presence of an inhibitor of P-450E, 7,8-benzoflavone (7,8-BF). Greatly reduced hepatic AHH activities in females coincided with the onset of vitellogenesis; however, a comparison of female starry flounder bearing yolky eggs from the two sites during several successive reproductive seasons indicated significantly greater AHH activity in those caught at Bk than those from SP. There was a linear relationship between hepatic AHH activity and its inhibition by 7,8-BF in all P. stellatus assayed and more than 98% of individuals caught in San Francisco Bay had hepatic AHH activites that were suppressed by 7,8-BF. Therefore, widespread induction of hepatic microsomal P-450 by PAH-type compounds in San Francisco Bay is indicated and, further, P-450 induction is apparent in female starry flounder in a portion of San Francisco Bay during gametogenesis and the time of spawning.