Kinetic studies of autologous mixed lymphocyte reaction (AMLR) over 7 days were made in 86 patients with various connective tissue diseases. None was receiving any treatment and each disease group was controlled with age-sex matched healthy controls. There were exceptions, but, as a rule, SLE patients (n = 22) had decreased responses on days 6-7. This was more apparent in patients with active disease than in those with inactive disease. Patients with scleroderma (n = 21) had early (day 4) proliferative responses. Half of the patients with RA (n = 14) had early (day 3) proliferation, but as a group they had normal increase in 3HtdR uptake on day 7. Patients with primary Sjögren's syndrome showed flat curves throughout and no significant proliferation on days 6-7 of culture. The pattern found in patients with mixed connective tissue disease (n = 11) was also peculiar in that they had peak proliferative responses on day 3 and normal 3HtdR uptake on days 6 and 7 of the AMLR. The number of patients with dermatomyositis or polymyositis was small (n = 6), but they showed a significant mean decrease in uptake on days 6-7. Studies using subpopulations of stimulatory cells further indicate that these patterns reflect immunoregulatory disturbances peculiar to each disease.