Epistasis plays a role in determining the phenotype yet quantitative trait loci (QTL) mapping has uncovered little evidence for it. To address this apparent contradiction, we analyzed interactions between individual Lycopersicon pennellii chromosome segments introgressed into an otherwise homogeneous genetic background of L. esculentum (cv. M82). Ten different homozygous introgression lines, each containing from 4 to 58 cM of introgressed DNA, were crossed in a half diallele scheme. The 45 derived double heterozygotes were evaluated in the field for four yield-associated traits, along with the 10 single heterozygotes and M82. Of 180 (45 x 4) tested interactions, 28% were epistatic (P < 0.05) on both linear and geometric scales. The detected epistasis was predominantly less-than-additive, i.e., the effect of the double heterozygotes was smaller than the sum of the effects of the corresponding single heterozygotes. Epistasis was also found for homozygous linked QTL affecting fruit mass and total soluble solids. Although the frequency of epistasis was high, additivity was the major component in the interaction of pairs of QTL. We propose that the diminishing additivity of QTL effects is amplified when more loci are involved; this mode of epistasis may be an important factor in phenotype canalization and in breeding.