The effect of systemic administration of 16,16-dimethyl prostaglandin E2-methyl ester (di-M-PGE2) on the growth of B-16 melanoma tumors was studied in C57BL/6J mice. Daily i.p. injection of 5 .mu.g of di-M-PGE2 commencing on the day of tumor inoculation with 105 and 106 viable cells delayed appearance of tumors. For the smaller tumor inoculum, it also increased median survival among treated mice from 23 to 33 days. Di-M-PGE2 treatment of mice with established tumors caused significant inhibition of tumor growth, as measured by a number of parameters including tumor diameters and volumes. At the time of sacrifice, di-M-PGE2-treated mice had tumors that were an average of 32% smaller (by weight), contained 60% fewer melanoma cells and had higher concentrations of cyclic[c]AMP and cGMP (+225% and +100%, respectively).