We used differential screening to isolate a full-length dehydration-responsive cDNA clone encoding a hydrophobic late embryogenesis abundant (LEA)-like protein from PEG-treated hot pepper leaves. Named CaLEA6 (for Capsicum annuum LEA), this gene belongs to the atypical hydrophobic LEA Group 6. The full-length CaLEA6 is 709 bp long with an open reading frame encoding 164 amino acids. It is predicted to produce a highly hydrophobic, but cytoplasmic, protein. The putative M(r) of CaLEA6 protein is 18 kDa, with a theoretical pI of 4.63. Based on our Southern blot analysis, CaLEA6 appears to exist as a small gene family. CaLEA6 was not expressed prior to any treatment, but its transcript was rapidly and greatly increased following trials with PEG, ABA, and NaCl. Chilling also induced its rapid induction, but to a much lesser extent. Accumulation of CaLEA6 protein occurred soon after NaCl applications, but considerably delayed after treatment with PEG. Tobacco plants that overexpressed CaLEA6 showed enhanced tolerance to dehydration and NaCl but not to chilling, as defined by their leaf fresh weights, Chl contents, and the general health status of the leaves. Therefore, we suggest that CaLEA6 protein plays a potentially protective role when water deficit is induced by dehydration and high salinity, but not low temperature.