In the present study, we investigated the effect of interleukin-4 (IL-4) on metalloproteinase 1 (MMP-1/tissue collagenase) production in human rheumatoid synovial fibroblasts. Northern blot analysis revealed that addition of IL-4 with or without histamine stimulated the cells to increase the amount of proMMP-1 mRNA, and the IL-4 with histamine addition resulted in a 3.3-fold increase compared with histamine only. Furthermore, IL-4 itself stimulated the expression of histamine H1 receptor mRNA. These results suggest that IL-4 may play an important role in joint destruction in RA.