Levels of serum aminoterminal propeptide of type III procollagen were measured in 170 patients with psoriasis (49% with coexistent psoriatic arthritis) who had liver biopsies performed during or before treatment with methotrexate or, in some cases, with retinoids. Psoriasis patients with fibrosis or cirrhosis in their liver biopsy specimens had a significantly higher mean serum aminoterminal propeptide of type III procollagen than did patients without fibrosis and without arthritis. Only 4% of patients without cirrhosis or fibrosis and no arthritis had an elevated serum aminoterminal propeptide of type III procollagen. In contrast, 38% of patients with psoriatic arthritis had an increased aminoterminal propeptide of type III procollagen in the absence of detectable liver fibrosis. It is concluded that the number of liver biopsies performed on methotrexate-treated psoriasis patients with or without arthritis may be reduced to a minimum as long as serum aminoterminal propeptide of type III procollagen is normal. Increased serum aminoterminal propeptide of type III procollagen in the absence of arthritis is a strong indicator of liver fibrogenesis and suggests the need for liver biopsy to monitor possible methotrexate-induced toxicity. In patients with psoriatic arthritis an increased aminoterminal propeptide of type III procollagen may be related to the joint disease. Patients with psoriatic arthritis and increased levels of aminoterminal propeptide of type III procollagen should therefore follow the established guidelines for the use of methotrexate in psoriasis.