Autologous mixed lymphocyte reaction (AMLR) studied at 7 days with cells from 20 scleroderma patients appeared decreased as compared to healthy matched controls. In kinetic AMLR studies with cells from 16 patients, this was found to result from the decline after an early proliferative response occurring on Day 4 (9 patients) or 5 (4 patients), whereas the other 2 had low responses throughout. As this early response may be anamnestic, kinetic studies lasting 12 days revealed a second proliferative response on the 9th or 10th day and the responses in allogeneic mixed lymphocyte cultures did not differ from those found in normal controls. These findings suggest either that autoreactivity between T and non T cells might have occurred in vivo in scleroderma patients and is recalled in the AMLR or that alterations of immunoregulatory cells permit this earlier activation in the system.