Abstract—Many organisms show latitudinal variation for various genetically determined traits. Such clines may involve neutral variation and originate from historical events or their maintenance may be explained by selection. For Drosophila melanogaster, latitudinal variation for allozymes, inversions, and quantitative traits has been found on several continents. We sampled D. melanogaster populations in Panama and along a transect of 40 latitudinal degrees on the west coast of South America. Negative correlations with latitude were found for AdhS and GpdhF allele frequencies and for the frequency of the cosmopolitan inversion In(2L)t in AdhS GpdhF chromosomes. A positive correlation existed between wing length and latitude. Significant correlations were found between these traits and climatic variables like temperature and rainfall. The observed clines show considerable resemblance to those found on other continents. Gametic disequilibrium between AdhS and GpdhF occurred predominantly at higher latitudes and was caused by the presence of In(2L)t. The reasons for the clinal distributions are discussed and it is argued that selection is the most likely explanation. However, the exact nature of the selective force and the interactions of allozymes with each other and with In(2L)t are complex and not fully understood. In tropical regions In(2L)t-containing genotypes have higher fitness than ST/ST and Adh and Gpdh hitchhike with the inversion, but there is also evidence for balancing selection at the Adh locus.