HLA-DR, HLA-DQ, and HLA-DP antigen expression was assessed by immunofluorescent flow cytometry on monocytes from 19 patients with active multiple sclerosis (MS), 19 with inactive MS, 7 patients with early active rheumatoid arthritis (RA), and 19 normal controls. Percentage positivity and median channel fluorescence (MCF) were determined after separation of the monocytes (TO) and following 48 h culture with (T48 + IFN) and without (T48) recombinant gamma interferon (rIFN-gamma). The percentage positivity of the cells was normal at TO for all groups of patients for each of the HLA types but statistically significantly increased above normal, on monocytes from patients with inactive MS, after culture with rIFN-gamma. At TO, the MCF values for HLA-DQ, and HLA-DP were statistically significantly increased above normal on monocytes from patients with active MS indicating some pre-programming of the cells in vivo. After culture, when the carry-over from baseline TO values was eliminated, the increment in MCF for HLA-DR, on monocytes from patients with inactive MS, was statistically significantly lower than normal in the non-gamma-IFN cultures but was normal in the presence of rIFN-gamma. Conversely, the increment in MCF for HLA-DP on monocytes from patients with active MS was significantly lower than normal after culture with rIFN-gamma. Therefore, the stimulation required to increase antigen density on cells already expressing antigen may be different to that required to stimulate de novo expression on negative cells. Both systems appear to be abnormal in MS, possibly reflecting differences in disease activity, while only one system appears abnormal in RA.