Abnormal polyclonal B cell activation has been demonstrated in patients with endometriosis. To determine whether the noted B cell abnormalities were primarily a feature of the disease endometriosis or its manifestations of infertility and pregnancy wastage, we investigated antibody profiles in 26 female patients with unexplained infertility (group A) and 24 patients with unexplained pregnancy wastage (group B) but without documented endometriosis. Group A and B patients exhibited an unusual incidence of gammopathies (10 of 26 patients in group A and 11 of 24 in group B), with a majority representing immunoglobulin M gammopathies. Mean immunoglobulin M values were significantly elevated in both groups (p less than 0.03 and p less than 0.05, respectively, Student t test), whereas immunoglobulin G was significantly increased only among group B patients (p less than 0.05, Student t test). Lupus anticoagulant by tissue thromboblastin inhibition test was abnormally elevated in 2 of 26 group A and 2 of 24 group B patients. Activated partial thromboplastin time values were abnormal in only 3 of 26 group A and 2 of 24 group B women. Immunoglobulin G, immunoglobulin M, and immunoglobulin A autoantibodies to two phospholipid antigens, five histones, and four polynucleotide autoantibodies were detected in 23 of 26 (88%) group A patients and 17 of 24 (70.8%) group B patients. We conclude that some patients with unexplained infertility and pregnancy wastage suffer from polyclonal B cell activation. It is therefore tempting to speculate that autoantibody abnormalities may be causally related to infertility and pregnancy loss.