Twenty-three striped skunks (Mephitis mephitis) without demonstrable antibodies in 1:25 serum dilution in the modified agglutination test (MAT) were fed sporulated Toxoplasma gondii oocysts (9 skunks) or tissue cysts (10 skunks), and 4 skunks (controls) were not fed T. gondii. Skunks were bled before feeding T. gondii, 10 and 23–25 days postinoculation (PI). All 9 seronegative skunks fed oocysts died of acute toxoplasmosis between 7 and 19 days PI; T. gondii tachyzoites were found in histological sections of many tissues. One of the 10 skunks fed tissue cysts and 1 of the 4 controls also died of acute toxoplasmosis days 19 and 20 PI; these animals probably became infected by ingestion of unexcysted oocysts passed in feces of skunks fed oocysts that were housed in the same room that skunks fed tissue cysts were housed. The remaining 9 skunks fed tissue cysts and the 3 controls developed only a mild illness and were killed in good health on days 23–25 PI. Antibodies to T. gondii were not found in 1:25 serum dilution of any of the 19 of 23 skunks that were alive on day 10 PI; 12 of 13 skunks had antibodies (MAT 1:80 or higher) on the day they were killed. Antibodies were not found in 1 skunk. Results indicate that skunks can develop IgG antibodies to T. gondii within 3 wk PI, and primary toxoplasmosis can be fatal in skunks.