Helper T-cell function was evaluated in 34 children infected with human immunodeficlency virus type 1, by assessing interleukin-2 production after stimulation of peripheral blood mononuclear cells with recall antigens (influenza virus, tetanus toxoid), allogeneic HLA, and phytohemagglutinin. In addition, helper T-cell function was correlated retrospectively with the incidence of opportunistic and bacterial infections. Four patterns of helper T-cell function were observed: (1) 7 (21%) of the 34 children responded to all stimuli, (2) 7 (21%) of them responded to alloantigens and phytohemagglutinin but not to recall antigens, (3) 7 (21%) responded to phytohemagglutinin but not to recall antigens or alloantigens, and (4) 13 (37%) did not respond to any of these stimuli. There were no significant differences related to different routes of acquisition among patients. Patients with functional helper T-cell defects had a history of more opportunistic (p=0.03) and bacterial (p<0.001) infections than did patients with intact helper T-cell function. Thus distinct patterns of helper T-cell dysfunction exist in children infected with human immunodeficiency virus type 1 and correlate with higher frequency of infections. Comparisons of in vitro helper T-cell responses to these stimuli may be useful for detecting early functional helper T-cell defects and for monitoring progression of disease.