Spontaneous lymphocyte proliferation (SLP), as a measure of the autologous mixed-lymphocyte reaction (AMLR), was used to detect possible systemic immunoregulatory differences between periodontally-diseased subjects and age-matched controls. Forty-four subjects formed four groups; young-healthy (YH), young-diseased (YD), old-healthy (OH) and old-diseased (OD) based on clinical examination to assess loss of attachment and bleeding on gentle probing. The mean loss of periodontal attachment for the YD, OH and OD groups was 5.9, 3.3 and 6.0 mm respectively, and the mean bleeding index was 0.39, 0.18 and 0.44. Their SLP was assessed using peripheral-blood mononuclear cells on days 3, 5, 7, 9 and 11 in culture. The peak response for the YH group occurred at day 7; that of the OH group was not until day 9, suggesting that age may alter the kinetics of the reaction as a delay in peak responsiveness. Using log transformation, to reduce individual variations within each group, SPL of peripheral-blood mononuclears from diseased subjects was depressed at day 7 for the young age group (p less than 0.01) and at day 9 for the older group (p less than 0.05). Not all diseased subjects had a depressed response, suggesting that SPL per se may reflect current rather than past disease activity. It seems that SPL could identify particular disease groups provided age and time of peak responsiveness are taken into account.