Polymorphism of the circumsporozoite protein (CSP) of Plasmodium malariae was characterized by comparing gene sequences of twelve field isolates obtained in Yaoundé, Cameroon, Central Africa, and one clinical isolate originating from Côte d'Ivoire, West Africa. The length of the CSP gene ranged from 1266 to 1302 bp. The size polymorphism was due to variation in the number of tandem repeat units. All P. malariae isolates displayed a highly conserved 5' non-repeat region. Seven non-synonymous and two synonymous nucleotide variations were observed in the 3' non-repeat region. In the deduced amino acid sequence the repetitive sequences consisted of a varying number of major (Asn Ala Ala Gly (NAAG); range between 42 and 46 units) and minor (Asn Asp Ala Gly (NDAG) or Asn Asp Gln Gly (NDEG); n = six or seven units) tetrapeptide units. None of the isolates had an identical sequence at nucleotide level. These findings suggest that polymorphism in CSP is essentially limited to the tandem repeat domain.