Anopheles mascarensis De Meillon, 1947, a mosquito that is native to Madagascar, is reported for the first time to act as a vector of Plasmodium falciparum malaria. From September 1989 to March 1990, 2, 499 An. mascarensis specimens from different regions of Madagascar were tested by an enzyme-linked immunosorbent assay (ELISA), using monoclonal antibodies against the circumsporozoite (CS) protein of the four human species of Plasmodium. The salivary glands of 237 specimens were also dissected. Fourteen of 1, 864 specimens obtained from Sainte Marie island on the Malagasy east coast were found by ELISA to be positive for the CS protein of P. falciparum. In addition, two of 237 specimens that were dissected were observed to have sporozoites in the salivary glands. These sporozoites were identified as P. falciparum by ELISA. In the other regions studied, no positive specimens were found. Due to observed behavioral differences between east coast and highland populations of An. mascarensis, the possible presence of a species complex is discussed.