Thinning of the dermis is the principal histological change in atrophic skin disorders and aged skin. It is caused due to a decreased amount of collagen in the dermis. Macrolides have been reported to exert various pharmacological activities, including anti-inflammatory activity, tumor angiogenesis inhibition and growth inhibition of fibroblasts, in addition to antimicrobial activity. In this study, we investigated the effects of erythromycin A (EMA) and its new derivative EM201 on type I collagen production by cultured dermal fibroblasts. Dermal fibroblasts were cultured with 10(-9) M-10(-5) M EMA or EM201, and collagen production was measured by incubation with radioactive proline, SDS-polyacrylamide gel electrophoresis and fluorography. mRNA levels were measured by Northern blots analysis, and to investigate transcriptional levels luciferase assays were also performed. The results showed that both EMA and EM201 increased collagen production and type I collagen mRNA level (to a maximum of 200% with EMA and 250% with EM201) in a dose-dependent manner in cultured dermal fibroblasts. Transcription of the type I collagen gene was also increased by both macrolides. These results suggest that EMA and EM201 have the potential to improve the thinning of the dermis in atrophic skin disorders and aged skin.