Type II alveolar cells are the primary site of synthesis of disaturated phosphatidylcholine (DSPC), the major component of pulmonary surfactant. Recent research indicates that lipid soluble agents may affect fetal lung development following maternal exposure. Since surfactant is primarily lipid in nature, potential exists that any one of these agents may alter surfactant metabolism. [Delta]9-tetrahydrocannabinol (THC), a lipophilic cannabinoid found in marijuana, has been shown to affect many cellular processes including enzyme activities, alterations in the structure of cytoskeletal elements and macromolecular synthesis. Recently, a cannabinoid receptor has been identified in type II cells. The present study examines the effects of THC on surfactant phospholipid synthesis and secretion in isolated fetal type II cells. Freshly isolated and cultured fetal rabbit type II cells were incubated with THC and [3H]choline over various times. Intracellular levels of radiolabeled DSPC were determined. [3H]DSPC levelsin both freshly isolated and cultured type II cells decreased upon cellular exposure to THC in a time and dose-dependent manner. Further studies examined the mechanism through which THC affects the synthesis of DSPC. (Abstract shortened by UMI.)