Improved methods for separating B and T cells have made it possible to assess the functions of these cells. These techniques have been used to study the T dependence of B-cell immunoglobulin production in response to pokeweed mitogen. In the present study they have been used to reinvestigate the pathogenesis of" variable" primary hypogammaglobuliaemia. Twelve patients were studied by separating their B and T cells and culturing them with normal cells. The results show that none of the patients have normal B cells. In cultures containing high ratios of T cells to B cells we have found a marked reduction in B-cell immunoglobulin production both with T cells from normal donors and from patients. T cells from all but one of the patients helped immunoglobulin production and reduced T helper activity was only seen in patients whose B cells were very abnormal. The results suggest that a B-cell defect is the cause of the low serum immunoglobulin in all the patients we have studied.