Serum alpha-1-acid glycoprotein (AGP) concentration and its microheterogeneity were measured in 46 patients with major depressive disorder and in 20 age- and sex-matched controls. The changes in major microheterogeneity of AGP were expressed as reactivity coefficient (AGP-RC). Also measured were the levels of C-reactive protein as well as leukocyte, neutrophil and monocyte counts. The results obtained showed that two thirds of the depressed patients studied, exhibited some immune disturbances during acute episode: first with a high AGP and high AGP-RC, and secondly with a low AGP-RC. The patients with the highest AGP-RC and higher AGP values had a longer duration of the illness and of the last depressive episode, a higher resistance to previous treatments, and a higher monocyte count. The character of the changes in the microheterogeneity of AGP bears some similarity to those observed in other diseases with immunological disturbances.