The concentration of 12 component and four control proteins of the complement system was measured in serum from 43 children with a nephrotic syndrome, which subsequently proved to be steroid-responsive, and from 13 children with focal glomerulosclerosis (FGS) and was compared with values from 197 normal subjects. Of classical pathway complement components, 40% of patients had low C1q levels and 20%, low C2 levels. Mean serum levels of C1s, C4, C1INH, and C4bp were elevated. Of alternative pathway components, factors B and I were low in one third, while levels of C3 and H were commonly elevated. Of the terminal components, only C8 and C9 were low. In five patients with FGS with hypoalbuminemia without edema, all component levels were normal. With the exception of C1q, C1s, and C8, high molecular weight (mol wt) components were in high concentration and low mol wt components in low concentration. The three exceptions may be explained by the subunit structure of C1 and C8. From a practical standpoint, the study indicates that edematous patients with a nephrotic syndrome may have low serum levels of C1q and C2, simulating classical pathway complement activation such as commonly occurs in glomerulonephritis. However, low levels of C4, and possibly C1s, can be used as indicators of classical pathway activation since their levels are not reduced by a nephrotic syndrome.