A clinical phase I-II evaluation of 2-amino-1,3,4-thiadiazole (A-TDA) administered daily, twice a week, or weekly was undertaken, in which 71 patients were treated with a range of doses from 2 mg/m2 to 200 mg/m2. Pharmacokinetic studies employing high-performance liquid chromatography (HPLC) demonstrated a terminal (beta) serum half-life of 2.19 h. Stomatitis, dermatitis, nausea, vomiting, and lethargy were observed. No significant leukopenia or thrombocytopenia, however, was noted. A-TDA administration led to hyperuricemia, which was adequately controlled with concurrent administration of allopurinol. Antitumor responses included one partial response in a patient with large cell carcinoma of the lung and three objective responses (2 non-small cell lung and 1 squamous cell carcinoma of the esophagus). Two patients with adenocarcinoma of the lung had a marked improvement of psoriasis during A-TDA therapy. Further phase II studies in patients with cancer and trials in patients with psoriasis are recommended.