As an early step in examining the factors that regulate synthesis of the IgA subclasses, IgA1 and IgA2, we determined the serum levels of IgA1, IgA2 and total IgA in 50 normal adults, 20 patients with systemic lupus erythematosus (SLE), and 11 patients with liver disease. A quantitative solid phase radioimmunoassay using subclass specific monoclonal hybridoma antibodies was used. Within the normal population there were large variations in the concentrations of IgA1 and IgA2. The levels of IgA1 and IgA2 in samples from males were not significantly different from those from females. However, the mean concentration of IgA1 in samples from Blacks was significantly lower than that from Caucasians, P less than 0.005. In the control population IgA2 constituted from 6 to 35% of the total serum IgA and the levels of IgA1 did not correlate with the levels of IgA2. The mean IgA1 and total IgA in samples obtained from patients with SLE were significantly higher than those from the normal population (P less than 0.0001) although there was no significant difference in the levels of IgA2 in the two groups. In the samples obtained from patients with liver disease both IgA1 and IgA2 were markedly elevated and the levels of IgA1 did correlate with the levels of IgA2. These results indicate that the serum levels of IgA1 and IgA2 are controlled by factors that influence each subclass independently as well as factors that affect each subclass equivalently.