A retrospective examination was made to determine parasitemia and episodes of fever in 97 patients, previously infected with Plasmodium malariae, P. ovale, and/or P. vivax, who were reinfected with P. falciparum for treatment of neurosyphilis, the standard treatment at the time. Data were collected at the National Institutes of Health laboratories in Columbia, South Carolina and Milledgeville, Georgia during the period 1940 to 1963. Results were compared with observations recorded for patients following primary infection with P. falciparum. The mean daily percentage of patients with fever > or = 101 degrees F during the first 20 days of primary infection with P. falciparum was 42.4; the percentage with fever > or = 104 degrees F was 19.9%. Those previously infected with P. ovale, P. vivax, and P. malariae had mean daily percentages of fever > or = 101 degrees F and > or = 104 degrees F of 39.1% and 14.8%, 39.1% and 19.4%, and 28.4%, and 11.3%, respectively. Previous infection with P. ovale or P. vivax had little, if any, effect on subsequent clinical malaria due to P. falciparum, whereas infection with P. malariae resulted in reduced frequencies of fever. A similar comparison was made for parasite counts > or = 1,000/microl and > 10,000/microl. The percentages for 268 patients during the first 20 days of primary infection with P. falciparum parasite counts > or = 1,000/microl and > or = 10,000/microl were 58.2% and 29.9%, respectively. Those previously infected with P. ovale, P. vivax, and P. malariae had mean daily percentages of parasitemia > or = 1,000/microl and > or = 10,000/microl of 58.0% and 24.3%, 57.3% and 31.1%, and 45.9% and 19.0%, respectively. Previous infection with P. malariae resulted in a reduction in the frequency of high-density parasitemia (> or = 10,000/microl) as well as an asexual parasite count > or = 1,000/microl. These results suggest that P. falciparum and P. malariae share common antigens that are able to induce parasitologic and clinical protection when infection with P. falciparum follows that with P. malariae. The results did not suggest that protection to P. falciparum is provided by previous infection with P. ovale or P. vivax.