In 60 patients (11 males, 49 females aged 25-66 years) in the acute phase of major depression and prior to starting pharmacotherapy Creactive protein (CRP) and alpha-I-acidic glucoprotein (AGP) levels, as well as AGP microheterogeneity were checked. In the group under study 34 patients met the criteria for drug-resistance (no satisfactory results had been obtained in two previous successive pharmacological treatments). These patients, as compared to the other 26 subjects, were characterized by a longer duration of both the disease from the onset, and of the acute phase. A comparison of the two groups revealed that drug-resistant patients had higher AGP serum levels, higher values of the AGP microheterogeneity index, and a larger number of monocytes than had the remaining subjects. Changes found in patients with refractory depression may be interpreted as manifestations of immunological hyperactivation. This might suggest that signs of such hyperactivation are associated with reduced efficacy of medication in patients with major depression.