Dysfunction of T-cell mediated immunity, which is indicated by deficient production of interleukin-2 (IL-2) and elevated levels of the soluble interleukin-2 receptor (sIL-2R), has been consistently demonstrated in schizophrenia. Recent studies on interferon-gamma (IFN-gamma), a cytokine which is also produced by T-helper cells, have indicated a lowered production in acute schizophrenia. It is not known whether this deficit is restricted to cases of acute schizophrenia or whether it is also present in residual schizophrenia and in first degree relatives, and therefore might be associated with genetic liability to the disease. We investigated 27 individuals (schizophrenics and first degree relatives) of 6 families with multiple occurrence of schizophrenia and 27 age- and sex-matched healthy controls. The production of IFN-gamma was lowered only in the acutely ill schizophrenic individuals, when compared to both controls and first degree relatives. In the context of current knowledge, this result indicates that the production of IFN-gamma can be discussed as a marker of acute exacerbation of schizophrenia, but it is not likely to represent a phenotypic marker of a genetic trait associated with the disease.