Human immunodeficiency virus type 1 can generally use CCR3 and CCR5 for cell entry. We show that envelopes with novel phenotypes arise during "coreceptor switch": one loses the ability to use CCR3 (R5-only phenotype), and another gains use of CXCR4 in addition to CCR5 and CCR3 (R3/R5/X4-using phenotype). The envelope determinants for CCR3 use mapped to three amino acids. One, N356 in conserved region 3, is a potential glycosylation site and has not previously been associated with coreceptor use. The other two, R440 and N448 in conserved region 4, are proximal to but distinct from residues already identified as being important for CCR5 binding.