Measles is associated with a vigorous antibody response without production of significant measles virus-specific delayed type hypersensitivity. Generalized disruption of immune responses also occurs during measles, including depressed skin test responses and decreased in vitro lymphocyte proliferation to mitogens. To determine if preferential activation of a subset of CD4 cells might explain these observations, the patterns of cytokines produced in vivo and in vitro during measles were determined. Soluble CD4 was elevated in plasma at all times. Interleukin (IL)-2 was increased in plasma during and shortly after the clearance of the rash and then declined. Plasma IL-4 became elevated after resolution of the rash and remained elevated in some patients through the 7-week study period. Mononuclear cells proliferated poorly in response to stimulation with anti-CD3 and produced low levels of IL-2 and interferon-gamma and high levels of IL-4 and IL-6 in vitro. The defect in lymphoproliferation during convalescence was partially corrected by in vitro neutralization of IL-4. Preferential activation of type 2 cells late during measles may explain the predominant humoral immune response and the generalized suppression of cellular immune responses.