We conducted linkage analyses of immunoglobulin G heavy chain marker (Gm) phenotypes and multiple sclerosis (MS) in 30 families, each having at least two first-degree relatives with definite/probable MS. These families yielded positive evidence for linkage to human leukocyte antigen (HLA) loci in previous analyses. In the present analysis, however, the results for Gm were negative. Most lod scores were negative, particularly at the smaller recombination values (theta). We explored the possibility of heterogeneity by subgrouping our data on the basis of specific HLA types (A3, B7) and Gm types (Gm1, Gm1,2) within the pedigrees. The results were again negative with no substantial differences in estimates of theta between subgroups.