The effect of dietary wheat gluten on liver and spleen lipogenesis in rats was studied in vitro and in vivo. Weanling rats were fed for 2 or 3 weeks an experimental diet containing wheat gluten as the only protein source and compared to other rats fed a casein control diet. Rats fed gluten showed enhanced in vitro lipogenesis as measured by conversion of (1(-14) C)-acetate into liver and spleen lipids. These results indicated that the gluten-fed rats had a significantly higher hepatic capacity than the control rats to synthesize all lipid classes. On the other hand, the in vivo study of hepatic lipogenesis showed smaller differences between the group fed gluten and that fed casein. This suggests that the accumulation of lipids in fatty livers of gluten-fed rats is mostly due to increased rate of biosynthesis and not a result of impairment in the lipids' transport system. In the spleens of the gluten-fed groups, the enhanced in vitro lipogenesis was also found in vivo, indicating that accumulation of lipids in fatty spleens may be a result of biosynthesis only, with no other effects that can take place in vivo.