Susceptibility to the development of asthma and other atopic diseases is known to be associated with genetic components. Several investigators have linked the tumor necrosis factor (TNF) genes and nearby markers located on chromosome 6p to atopy and asthma. Recent study has demonstrated that the TNF-alpha*2 allele of a polymorphism in the TNF-alpha; gene promoter region (G-308 A) is associated with a higher risk for the development of atopy in Spanish patients. The objective of this study was to evaluate the possible role of two described bi-allelic polymorphisms in the TNF locus alpha;a G to A transition at position -308 in the promoter region of the TNF-alpha gene and an NcoI restriction fragment length polymorphism (RFLP) in the first intron (+252A/G) of the LT-alpha(TNF-beta) gene in atopic diseases in a Czech population. We investigated the distribution of these polymorphisms in a case-control study. The genotypes were determined in 151 patients with atopic asthma and 155 random-sampled control subjects. The genotype frequencies for both polymorphisms were similar in cases and controls. No significant differences in allele frequencies were found between either of the patients groups and the reference subjects. Similarly, there were no associations of any of the examined variants of the TNF genes with total IgE, specific IgE or pulmonary function tests in patients with allergic diseases. We conclude that these polymorphisms of the TNF genes are unlikely to contribute to atopic disease risk in our population. Significant associations which have been reported in other studies may express genetic heterogeneity of these complex diseases.