The diversity of spatial patterns of 61 allele frequencies for 20 genetic system s (15 loci) in Italy is presented. Blood antigens, enzymes, and proteins were analyzed. The total number of data points over all systems and localities was 1119. We used homogeneity tests, one-dimensional an d directional spatial correlograms, and SYMAP interpolated surfaces. The data matrices were reduced by clustering techniques to reveal the principal patterns. Only a few allele frequency surfaces are strongly correlated across loci. All systems but one (ADA) exhibit significant heterogeneity in allele frequencies among the localities. Significant spatial patterns are shown by 27 of the 61 surfaces. Only one pattern (cde; system 4.19) is clinal; an other (PGM1) exhibits a pure isolation by distance pattern; the others show long-range differentiation in addition to the short-distance decline of autocorrelation expected under isolation by distance. There is a marked decline in overall genetic similarity with distance for most variables. T he 27 spatially significant alleles in Italy are also significantly patterned in Europe, but in all but 2 cases the countrywide and continent-wide patterns differ. The Italian patterns are due to forces specific to Italy. Differential selection for alleles associated with malaria is still evident. Whereas short-range differentiation can be explained by isolation by distance, long-range differentiation appears to be due to demographic changes in certain populations that may be maintained by physical and linguistic isolation.