To elucidate the role of heat-shock proteins (HSP) in the formation of resistance to extreme factors and in the development of organismic and cell response to these factors, thermotolerance in a Drosophila melanogaster line with defective HSP synthesis was studied with regard to several criteria: (1) survival of adult females; (2) damage to egg chambers in ovarioles; (3) dynamics of oviposition; (4) frequency of loss and non-disjunction of sex chromosomes in meiosis of females exposed to a heat shock (HS). According to all these criteria, the l(1)ts403 females were more sensitive to at 37°C for 1 h (HS37) than the females of the wild-type line Canton S. Only the data on the first three aforementioned parameters were indicative of thermotolerance development. In flies exposed to HS35 followed by HS37, a decrease in nondisjunction and loss of sex chromosomes in the three- and four-day ovipositions was observed as compared to the flies exposed to HS37 only. This can be explained by the differences in oviposition dynamics and, consequently, in the realization rate of the oogenesis stages in these two experimental variants. The pleiotropic effect of the l(1)ts403 mutation that led to a disturbance in HSP gene expression at the posttranscriptional level and to an increase in the frequency of sex chromosome nondisjunction in the meiosis of females exposed to HS37 suggests that these processes were connected. As no thermotolerance was revealed by studying the sex chromosome nondisjunction, but thermotolerance was found by estimating the other parameters, we suggest that the product of the gene studied is involved in a signal system operating at a stage that precedes the HS-induced changes in the translation and division apparatuses of a cell.