To investigate the effect of spaceflight on cell mediated immunity we tested delayed-type hypersensitivity (DTH) in 5 cosmonauts on three missions in the orbital space station MIR. DTH was determined by the intradermal application of seven antigens and a control using the standardized Multitest Mérieux. This multiple prick puncture test was applied prior to, during, and following missions, which lasted for up to 177 d. In four of the five cosmonauts, reaction scores of DTH-responses below the warning level were noted during flight (two subjects) or following landing (two subjects). In-flight reductions of DTH-responses were possibly induced by a series of stressful extravehicular activities and recovered to normal levels after landing. The results confirm earlier observations of a decreased lymphocyte function following spaceflights determined by means of mitogenic responsiveness of lymphocytes. Thus, the notion of a possibly impaired cell-mediated immunity under stress in association with spaceflight gains further support.