AIM: To test the hypothesis that phenotypic diversity in isolated human populations is decreased in comparison with general outbred population because of reduced genetic and environmental diversity. To demonstrate this in populations for which reduced genetic and environmental diversity had already been established, by studying the amount of variation in plasma lipid levels. ----- METHODS: Fasting plasma lipid levels (cholesterol, triglycerides, low density lipoprotein [LDL], and high density lipoprotein [HDL]) were measured in randomly selected 300 inhabitants from 2 isolated human populations, the island of Rab and the neighboring islands of Vis and Lastovo, Croatia. The populations were chosen based on previous analyses of genetic diversity and lifestyle patterns, which were shown to be both less diverse and more uniform than the general Croatian population. We studied whether the 25'-75' and 5'-95' interpercentile ranges in observed values were consistently smaller in 2 samples of 300 examinees from isolated populations in comparison with nearly 6000 examinees from an earlier study who were demographically targeted to represent the larger Croatian population. ----- RESULTS: General population had much wider range of observed values of triglycerides and HDL than both isolated populations. However, both isolated populations exhibited greater extent of variation in the levels of LDL, while the ranges of cholesterol values were similar. ----- CONCLUSION: Although reduced genetic and environmental diversity in isolated human populations should necessarily reduce the variance in observed phenotypic values, it appears that specific population genetic processes in isolated populations could be acting to maintain the variation. Departure from the Hardy-Weinberg equilibrium due to consanguinity, sub-structuring and differentiation within the isolates, and increased rate of new mutations could theoretically explain this paradox.