1. Methotrexate handling has been studied in four patients with psoriasis and eleven patients with neoplastic disease. 2. Methotrexate levels in serum, tears and saliva were measured by radioimmunoassay while protein binding studies were performed by continuous ultrafiltration. 3. There was a close correlation between methotrexate concentrations in tears and serum (P less than 0.001, r = 0.714). Parotid salivary and serum methotrexate levels were similarly correlated (P less than 0.001, r = 0.557) but not mixed salivary and serum levels (P greater than 0.1, r = 0.232). 4. The mean protein binding was 95.11% +/- 2.26 (s.d.) while the ratio of methotrexate levels in tears to the free serum methotrexate level was 1:1.04. The corresponding parotid salivary level: free serum level ratio was 1:18.11. 5. No relationship could be determined between the methotrexate levels in tears and conjunctivitis observed in some of the patients under study.