Estimates of the number of human genes that produce more than one transcript isoform through alternative mRNA splicing depend on the assumption that the observation of multiple transcripts from a gene can be attributed entirely to alternative splicing. It is possible, however, that a substantial proportion of cases where multiple transcripts have been observed for a gene result from differences between alleles. Many examples of genes that are spliced differently from different alleles have been reported but no systematic estimate of the proportion of alternatively spliced genes that are affected by such polymorphisms has been carried out. We find that alternative transcript isoforms are non-randomly associated with closely linked nucleotide polymorphisms, based on an integrated analysis of the dbSNP, dbEST and ASAP databases. From the observed level of association between transcript isoforms and polymorphisms, we estimate that 21% of alternatively spliced genes are affected by polymorphisms that either completely determine which form of the transcript is observed or alter the relative abundances of some of the alternative isoforms. We provide a conservative lower bound of 6% on this estimate and point out that alternative splicing cannot be confirmed absolutely unless more than one transcript is observed from the same allele.