Insulin receptors are present on fetal and newborn tissues in significantly greater numbers than on adult tissues. Recent studies have suggested that membrane fluidity, which is dependent upon lipid constituents, is important in regulating the appearance and behavior of insulin receptors. We have compared the lipid composition and fluidity as well as insulin receptor binding to monocytes from normal adults and full term normal infants.Newborn infants had significantly higher insulin levels than did fasting adults (17.4 ± 2.4versus9.8 ± 0.6 μU/ml;P< 0.001); despite this, cord blood monocytes showed significantly higher125I-insulin tracer binding than did those of adults (9.5 ± 0.51versus7.6 ± 0.45%/107cells;P< 0.02). From Scatchard analysis, it was evident that cord monocytes had greater numbers of both high (2.94versus1.25 x 10-10M-1) and low affinity (13.1versus8.57 x 10-10M-1) receptors than adult monocytes.Cord mononuclear cells had significantly lower phospholipid concentrations than adult cells (0.085 ± 0.012versus129 ± 0.012 mg/mg of protein;P< 0.025) and significant elevations of cholesterol/phospholipid ratios (0.520 ± 0.045versus0.354 ± 0.009;P< 0.005). Microviscosity determinations were performed using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene. Cord cells had significantly greater microviscosity values (fluorescence polarization) (0.339 ± 0.030versus0.186 ± 0.019;P< 0.005), compared to adult cells. For all subjects, a highly significant correlation was noted between cell microviscosity measurements (fluorescence polarization) and125I-insulin tracer binding to mononuclear cells (r= 0.72,n= 15,P< 0.005).The data support the concept that as membrane fluidity decreases (i.e.viscosity increases) intrinsic proteins including receptors are displaced outward, increasing their exposure to the aqueous environment.