The safety and immunogenicity of 20 and 200 ug doses of 2 yeast-derived malaria vaccines were evaluated in a phase 1 randomized clinical trial. Healthy adults (N=40) were given up to 3 monthly doses of alum-adjuvanted vaccine containing a 19kD fragment of MSP-1 (3D7 or FVO strain) fused to tetanus T-helper epitopes P30 & P2 (N=8 for each vaccine and dose group); 3 doses of hepatitis B vaccine (HBV) (N=4); or adult tetanus-diphtheria booster (Td) followed by placebo (N=4). The first 2 doses of vaccine were well tolerated. After the 3rd dose 3 subjects had hypersensitivity reactions. 2 (1-3D7, 1-FVO) developed bilateral injection site reactions, 1 with generalized skin rash. 1 subject given 200 ug of FVO had histamine-assd hypotension and flushing resulting in trial termination. 2 or 3 doses elicited =>4x increases in ELISA antibody to MSP-1 19 in 5/16 given 20 ug and in 8/16 given 200 ug; 0/8 given HBV or Td responded. Changes in adjuvant and/or schedule may improve the safety and immunogenicity of MSP-1 19 vaccines.