Cycloalkanes/naphthenes are constituents of complex hydrocarbon solvents, and hence an understanding of their toxicological profile is critical to establish safe limits for occupational exposures to these solvents. Although naphthenes are structurally related to and share a common metabolic fate with the straight and branched chain analogues, some toxicokinetic differences have been noted. The acute central nervous system response to volatile naphthenes in rodents has been shown to be slightly different compared to other alkane analogues. To determine whether these differences may extend to systemic effects with less volatile naphthenes, rats were exposed to 1500, 3000 or 6000 mg/m3 of a C9-C11 aliphatic solvent containing 70% naphthenes, for 90 days. Effects were limited to adaptive liver enlargement in both sexes and kidney toxicity in the male rat. For comparative purposes, the results from this study were compared to published reports of a complex hydrocarbon solvent with a higher proportion of volatile C5/C6 naphthenes and a mono-constituent naphthene (decahydronaphthalene). The results indicate that the systemic effects of naphthenes are similar to the straight and branched chain analogues and that the effects that are most relevant for human health evaluations of alkanes are acute central nervous system effects.