Cytokines like tumor necrosis factor (TNF), interferon‐γ (IFN‐γ), and interleukin‐1 (IL‐1) are known to interfere with the differentiation of cultured cell lines of adipocyte precursors. In the present study, the effect of mouse and rat IFN‐γ, as well as human IL‐1β, was investigated on rodent preadipocytes in primary cultures, either in the presence of fetal bovine serum (FBS, 10%) or in serum‐free defined medium. IFN‐γ exerted an antiproliferative action that was more pronounced when cells reached confluency than during the growth phase of the culture. Morphological observation and quantifications of undifferentiated and differentiating cells revealed that IFN‐γ caused a decrease in the proportion of cells devoid of lipid droplets which would correspond to fibroblast‐like cells, whereas preadipocytes remained unaffected. IFN‐γ induced a marked retardation of adipoconversion, resulting in a partial inhibition of lipoprotein lipase (LPL) activity and a severe decrease in glycerol‐3‐phosphate dehydrogenase (GPDH) activity. The antiproliferative and anti‐LPL effects of IFN‐γ were neutralized by adding anti‐IFN‐γ antibodies, while these antibodies prevented only partially the depressing effect of IFN‐γ on GPDH activity. Contrary to IFN‐γ, IL‐1β slightly enhanced the proliferation in preadipocyte cultures. IL‐1β also depressed adipoconversion, inhibited markedly LPL activity, and partially reduced GPDH activity. These results show that the influence of cytokines on adipoconversion observed in preadipocyte cell lines can be tound in normal preadipocytes in culture. © 1992 Wiley‐Liss, Inc.