Oral submucous fibrosis is a chronic disabling disease developing in up to 0.5% of the estimated 500 million habitual chewers of the "betel" quid. The quid, or chew, usually comprises a leaf of the Piper betel vine in which is wrapped fragments of the nut of Areca catechu, together with slaked lime and varied additives, including tobacco. The precise aetiology of oral submucous fibrosis (OSF) remains obscure, but epidemiological and animal studies have pointed to a close association with the prolonged usage of A. catechu nuts. Epithelial atypia and epidermoid carcinoma have been reported in 15% and 7%, respectively, of patients with established OSF. Preparations from varieties of A. catechu nuts have been tested for their ability to stimulate collagen synthesis in microwell cultures of human fibroblasts, using a pulse of 3H-proline and subsequent analysis of the cultures for radioactive collagen. Crude extracts of three varieties of areca nuts were extracted with ethanol and lyophilised before dilution in the culture medium. Control media contained identical concentrations of ethanol where appropriate. The three extracts at a concentration of 10 micrograms/ml stimulated collagen synthesis by approximately 150%, suggesting that this effect might be involved in the aetiology of oral submucous fibrosis.