Honn et al. [Science (Wash. DC), 212: 1270, 1981] have recently reported a 93% reduction in the development of metastases of B16 amelanotic tumor cells given i.v. following a single dose of prostacyclin (PGI₂) (100 µg) and theophylline (100 µg) 30 min prior to the injection of tumor cells. We have been unable to reduce pulmonary metastases induced by the i.v. injection of CT26 colon adenocarcinoma, Lewis lung carcinoma, or B16 amelanotic melanoma cells with a similar regimen. Thus, PGI₂ and theophylline given prior to injection of tumor cells and 2 hr postinjection had no effect on the number or volume of pulmonary tumor nodules for CT26 cells, using 15 experimental and 14 control animals; Lewis lung cells, using 14 experimental and 13 control animals; or B16 amelanotic cells, using 26 experimental and 12 control animals. The PGI₂ used was shown to be active in vitro, inhibiting tumor-induced platelet aggregation by all three tumors at 10^-9 m; and in vivo by inhibition of Lewis lung-induced thrombocytopenia at 1 hr, using 100 µg PGI₂ prior to the injection of tumor cells.