The surface of Pneumocystis carinii sp. f. carinii contains an antigen known as major surface glycoprotein (MSG), which is encoded by about 100 heterogeneous genes. Expression of MSG genes is not well understood. Previous work identified a sequence termed UCS, which is present at the beginning of nearly all MSG mRNAs, and which is likely to be involved in regulation of MSG gene transcription. Here we show that the UCS was present in one copy per haploid genome, but that different MSG genes were linked to the unique UCS locus in different members of a P. c. carinii population, predicting that individual organisms transcribe a limited number of MSG genes. This prediction was supported by indirect immunofluorescence observations. Comparison of three different populations of P. c. carinii showed that each contained a different set of MSG genes linked to the UCS, suggesting that UCS-MSG junctions are formed by recombination during population growth. Both the UCS and MSG genes were shown to be located at the ends of chromosomes, suggesting that the mechanism for UCS-MSG recombination is reciprocal exchange.