IgG class antibodies against human IgM were detected in a human subject up to a titer of 1:1024 against 5 of a group of 23 monoclonal Waldenström macroglobulins. Inhibition studies confirmed at least one antigenic determinant shared by the 5 IgMs. The determinant was present on the mu chain but required tertiary structure for its full expression. Inhibition of the reaction between the antibodies to IgM and erythrocytes coated with 2 of the 5 IgMs was obtained at titers of 1:2 to 1:16 with 51.0% of 300 normal sera (85.2% of sera from 122 Caucasian, 26.1% of sera from 23 Negro, and 27.7% of sera from 155 Japanese individuals). This inhibition was independent of the serum IgM concentration. Family studies indicated that the determinant was inherited according to basic Mendelian laws and appears to be the first allotypic marker on human serum IgM. We have designated it Mm 1.