A retrospective examination was made of archival data collected between 1940 and 1963 to determine the impact of reinfection of patients with Plasmodium vivax with homologous and heterologous strains of the parasite. Following reinfection of 14 patients with a homologous strain, the geometric mean maximum parasite count was reduced from 9,101/μL during the primary infection to 998/μL and the geometric mean daily parasite count for the first 20 days was reduced from 923/μL to 16/μL. Following reinfection of 22 patients with heterologous strains of P. vivax, the geometric mean maximum parasite count was 8,460/μL during the primary infection versus a secondary level of 9,196/μL and the geometric mean daily parasite count decreased from 847/μL/day to 335/μL/day. Reductions in fever episodes ≥101°F and ≥ 104°F appeared to be a more sensitive measure of clinical immunity. Fever episodes ≥104°F in patients with homologous strain reinfections decreased from 1.92 episodes per week to 0.18 compared with 1.24 to 0.57 in patients with heterologous infections. Fever episodes ≥101°F decreased from 2.98 to 0.60 in the homologous strain compared with 2.08 to 1.07 for the heterologous infections. The average maximum fever temperature in the homologous group was 106°F during the primary infection versus 103.4°F for the secondary infection compared with 105.8°F during the primary infections versus 105.6°F for the secondary infection in the heterologous patients.