A retrospective analysis was made of the parasitologic and fever records of 318 patients who had been infected with the El Limon, Santee Cooper, or McLendon strains of Plasmodium falciparum for treatment of neurosyphilis between 1940 and 1963 to determine the development of parasitologic and clinical immunity during primary infection. The presence of fever > or = 101 degrees F and > or = 104 degrees F, asexual parasite counts > or = 1,000 and > or = 10,000/microl, and gametocyte counts > or = 100/microl and > or = 1,000/microl are presented. The frequency of fever (number of patients with fever/number of patients remaining in study) for the first 100 days of patent parasitemia, the frequency of parasite counts > or = 1,000 and > or = 10,000/microl during the first 100 days of patent parasitemia, and the frequency of gametocyte counts > or = 100 and > or = 1,000/microl during the first 100 days of patent parasitemia are presented for 4 groups of patients: 1) sporozoite-induced and 2) trophozoite-induced infections requiring treatment during their primary attack, and 3) sporozoite-induced and 4) trophozoite-induced infections not requiring treatment during the primary attack. For each sporozoite-induced infection, the route of inoculation (bites or syringe), the species of mosquito used, the number of mosquito glands or bites, the intensity of salivary gland infection, and the length of the prepatent period are recorded. Prepatent periods for 109 sporozoite-induced infections ranged from 6 to 28 days. Patients with parasitologic or clinical findings that required suppressive, but non-curative treatment, during the primary attack had higher frequency of fever, parasitemia, and gametocytemia than patients not so treated. Fever was concentrated in the first 2 weeks of patent parasitemia although instances of fever were reported >100 days after infection. High-density parasitemia was also concentrated early in the infection; instances of parasite counts > or = 10,000/microl occurred > 75 days after infection. In conclusion, immunity to infection with P. falciparum was shown to develop rapidly. Following primary infection, clinical and parasitologic immunity was evident within 2-3 weeks following the detection of parasites in the peripheral circulation.