Coupled adult pairs of Schistosoma mansoni were incubated in medium containing either peripheral or portal serum from rat, rabbit, hamster or humans. Daily egg production was measured. In all cases egg production was significantly increased for pairs in the presence of portal sera compared with that in the presence of peripheral sera. Fractionation of rabbit portal serum according to molecular weight demonstrated that the most active component(s) were in the range of 2,000 to 50,000. These fractions were as effective in stimulating oviposition as whole portal serum. Conclusions: 1) portal serum factor(s) that stimulate S. mansoni oviposition are present in susceptible and non-susceptible hosts; 2) the molecular weight range for the active components is larger than would be expected for simple carbohydrates, amino acids or free fatty acids absorbed from the gastrointestinal tract.