Coccidioidomycosis is a fungal infection caused by Coccidioides species endemic to the southwestern United States, where it poses unique challenges for transplant recipients. Donor-derived coccidioidomycosis has been documented, but its risk of transmission is not known. We prospectively screened 568 healthy persons requesting evaluation for possible liver or kidney donation. Twelve (2.1%) of the 568 donor candidates were seropositive (11 initially and 1 with seroconversion and symptomatic illness within 1 week after negative screening). Three of these 12 patients proceeded to kidney donation, and a fourth patient proceeded to liver donation. None of the 4 transplant recipients received special coccidioidal prophylaxis, although all were administered fluconazole according to standard antifungal prophylaxis protocols. At follow-up (7-54 months), no coccidioidomycosis was identified in any recipient. The prevalence of coccidioidal antibodies was low among potential organ donor candidates, but the risk of donor-derived coccidioidomycosis remains unknown and further study is warranted.