Three murine PPAR (peroxisome proliferator activated receptor) genes were localised to chromosome 15 (PPARalpha), chromosome 17 (PPARß) and chromosome 6 (PPARgamma). The expression of the three PPAR RNAs was determined using a specific RNAase protection assay. In liver RNA, PPARalpha was expressed at the highest level, with twenty-fold lower levels of PPARß, and very low levels of PPARgamma. The three PPAR RNAs showed no sex-specific differences in expression, and the levels of these transcripts were unaffected by treatment of mice with testosterone or the potent peroxisome proliferator, methylclofenapate. In agreement with this data, the level of PPARalpha protein in liver was unchanged after treatment of mice with methylclofenapate. Investigation of the tissue-specific distribution revealed that the PPARalpha RNA was expressed at highest levels in liver, moderate levels in kidney and brown adipose tissue, and at low levels elsewhere. The PPARß was expressed at moderate levels in liver, and lower levels in other tissues, including brown adipose tissue. By contrast, PPARgamma RNA was expressed at low levels in liver or epididymal white adipose tissue and very low levels elsewhere, but was expressed at high levels in brown adipose tissue. The tissue distribution of these receptors suggests an important role in lipid metabolism and toxicity for individual members of the PPAR family. The expression of PPARalpha and ß RNAs was examined in thirteen strains of mice, and the levels of expression varied within a four-fold range. A polymorphism in the size of PPARalpha RNA from Swiss-Webster mice was detected, and shown to be due to a two base pair mutation in the 3' non-coding region of PPARalpha in Swiss Webster mice.