The skin window technic was utilized to determine the reactivity of patients with rheumatoid arthritis (RA) and acute post-streptococcal glomerulonephritis (APSGN) to human IgG (H-IgG). The response to H-IgG was compared in nine patients with RA, 20 patients with APSGN, and 10 normal individuals. All subjects were tested concomitantly with the saline solution used as solvent for H-IgG. The normal controls and five patients were challenged, in addition, with diphtheria-tetanus-pertussis antigen (DPT) to which they had previous prophylactic exposure. The following results were obtained: 1) Four patients with RA and nine patients with ASPGN responded with increased lymphocyte migration (more than 2 SD above the normal mean level) at nine and 12 hours. 2) The mean estimated immunogenic lymphocytosis (calculated substracting the lymphocyte counts of the saline skin windows) of both patient groups was significantly higher than that of controls at the same time intervals. 3) The response of normal individuals and patients to DPT was comparable in time of appearance and intensity to the response of patients to H-IgG. Our studies suggest that patients with RA and APSGN respond to H-IgG in a manner comparable to that observed with a known antigenic stimulus and support a clinical role for antiglobulin reactivity.