Recently, there have been some reports that depression may be accompanied by indices of polyclonal B cell proliferation. In order to examine whether depression is characterized by an altered B cell subset profile we determined the number and percentage of the following B cells: HLADR+, CD19+, CD20+, and CD21+. We found a significantly increased number of HLADR+ and CD19+ B cells in depressed subjects compared with normal controls. Depressed patients exhibited a significantly higher percentage of HLADR+ and CD21+ B cells than normal controls. The number of CD21+ cells and the percentage of CD19+ cells were higher in melancholics than in normal controls. The increase in the number of the various B cells was highly sensitive (63%) and specific (94%) for melancholia. Our results may indicate B cell proliferation in depression, and particularly in melancholia.