Mice thymus responses to algal yessotoxin (YTX)were examined by histochemical andimmunocytochemical procedures. Immunoreactivity fordifferent MW cytokeratins (CK) and for cytokines (IL-1a, IL-6, IL-8) was analyzed. Modifications ofparameters such as cell proliferation and cell deathwere also studied. Thymus from male swiss CD1 miceintraperitoneally injected with lethal (420 mg/kg) andnot-lethal (10 mg/kg) doses of YTX were examinedafter 2 and 24 hours, respectively. Histological studiesrevealed morphological modifications with both YTXdoses. Lethal treatment provoked changes in thecortex region that appeared less compact with lightareas containing a reduced number of thymocytes andlarge pale epithelial cells. An increased number ofmitotic as well as apoptotic phenotypes was alsoobserved. More severe damages were observed withthe lower YTX dose and after 24 h of treatment.Indeed, an increased number of apoptotic cells wasobserved mainly in cortico-medullary junction and inmedulla. Groups of flattened medullary epithelial cellsformed single or clustered round structures thatresembled Hassall’s corpuscles and containedheterogeneous secretory material and necrotic nuclei.The medullary epithelial cells were the most affectedcell population. These cells were arranged in a regularreticulum of stellate cells immunoreactive (ir) to highMW CKs, whereas after YTX treatment some cellsdecreased their ir and some others withdrewcytoplasmic projections modifying to strongly ir roundcells. The core of the newly formed medullarystructures and true Hassall’s corpuscles was alsostrongly ir to higher MW CKs. With regard to cytokineresponse, changes were observed in bothexperimental treatments in comparison to controls. Anhigher number of cells ir to IL-6 located at the corticomedullaryjunction and medulla was found, and theywere mostly dendritic cells, while IL-1 a and IL-8 ircells, observed in the cortex, decreased. The presentfindings, in disagreement with others reportinglittle or no toxic effects, indicate that YTXprovokes severe morphofunctional damage tothymic microenvironment.