Serum B-lipoproteins recently were reported to inhibit lymphocyte blastogenesis (Menchaca et al. Lancet 1:1085, 1980; McLeod et al. Ped. Res. 14:1012, 1980). This study further characterizes the inhibitory factors. Lymphocytes from normal donors were cultured in serum of 3 MCNS children in relapse or in normal serum (control) for 48 hours with phytohemagglutinin (PHA) and 3 H-thy-midine added for the last 6 hours. Heparin-Mn-precipitate(H-Mn-p) from MCNS serum showed 36% inhibition of PHA response. Sepharose 4b chromatography showed a large peak by O.D. at 280 nm (Mol. wt. 2 million). This fraction inhibited blastogenesis in proportion to amount added. Immunoelectrophoresis (IEP) revealed a B-lipoprotein and 2 non-lipid containing proteins. All the fractions obtained by density gradient separation at 100,000 × g for 18 hrs showed inhibition and contained lipids by IEP, but the least dense (d=1000-1005) showed only one precipitin line. Normal serum showed no inhibition. H-Mn-p from normal serum showed no peak and no effect on PHA response at any concentration tested. Based upon observations that an inhibitory factor of lymphocyte blastogenesis 1) was precipitable with heparin-Mn, 2) eluted from gel filtration at high molecular weight, 3) appeared in a low density fraction, and 4) was associated with presence of B-lipoproteins, it seems that either lipoproteins or lipoprotein-bound compounds are responsible for that inhibition.