In this investigation, human fetal intestine (17-20 wk) was used to study the synthesis of apolipoproteins (apo) A-I and B and its modulation by epidermal growth factor. Cultured jejunal explants were incubated with [3%S]-methionine, homogenized, immunoprecipitated and subjected to gel analysis. Radioactivity was detected mostly in apo A-I and, to a lesser extent, in both apo B-48 and apo B-100. However, apo B-48 was always the predominant form. The addition of EGF (100 ng/ml) resulted in a simultaneous decrease in apo B-100 synthesis and increase in apo B-48 production without a marked effect on apo A-I. Moreover, the incubation of jejunal explants with [14C] oleic acid documented the ability of fetal intestine to produce chylomicrons, VLDL, LDL and HDL. Therefore, the human fetal intestine has an efficient lipoprotein-lipid transport system and EGF is able to modulate levels of both apo B species as well as lipoprotein fractions.