Merbarone, 5-(N-phenylcarboxamido)-2-thiobarbituric acid (NSC 336628), is a derivative of barbituric acid and represents a unique class of antineoplastic agents. We treated 16 patients with advanced gastric carcinoma in a phase II study of merbarone. All patients were previously untreated with chemotherapy or biological therapy. The starting dose of merbarone was 1000mg/m2 infused over 24 hr for 5 consecutive days every 21 days. A median of two courses (range, 1-7) was given. None of the patients achieved a complete or partial response; however, 3 patients achieved a transient minor response. Toxicity was mild to moderate in most patients, but 1 patient died of treatment-related neutropenia and sepsis. Our data suggest that merbarone at this dose and schedule is inactive against gastric carcinoma. The evidence of minor response suggests that analog research may be worthwhile to pursue.