Human diploid fibroblasts (HDFs) from newborn foreskin constitutively express interleukin-1 (IL-1) mRNA and protein after completing at least 70% (approximately 40 population doublings) of their in vitro life span. This IL-1 in turn induces the synthesis of specific proteins in aging HDFs. To determine whether IL-1 expression may be promoted by in vivo aging, we analyzed the expression of IL-1 and of inducible mRNAs in HDFs from two normal individuals 55 and 92 years old and in HDFs from a patient with premature aging caused by Werner's syndrome. By reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), we detected expression of IL-1 alpha and beta mRNA and protein in early passage HDFs from both normal individuals and the Werner's syndrome patient. These HDFs also expressed the IL-1-inducible mRNAs for stromelysin, plasminogen activator inhibitor type 2, manganous superoxide dismutase, and collagenase. These results suggest that an age-dependent expression of IL-1 occurs either in vivo or after a few cell divisions in vitro. Therefore, the fibroblast phenotype is modified by the expression of IL-1-inducible genes during aging.