A3-year ecological study of small mammals was carried out in an endemic area for hantavirus pulmonarysyndrome in the state of Santa Catarina in Southern Brazil. A total of 994 rodents of 14 different speciescorresponding to the subfamilies of Sigmodontinae, Murinae, Eumysopinae, and Caviinae were capturedduring 2004–2006. Oligoryzomys nigripes and Akodon montensis were the most abundant species andshowed a clear seasonal pattern with higher population sizes during the winter. Rodent population out-breaks, associated within bamboo mast seeding events, were detected predominantly in areas wherehantavirus pulmonary syndrome cases were notified in the state. Antibody reactivity to Hantavirus wasdetected in five sigmodontine species: O. nigripes (39/435), A. montensis (15/318), Akodon paranaensis(4/37), Thaptomys nigrita (1/86) and Sooretamys angouya (1/12). The highest hantavirus antibody preva-lence occurred during the period of highest population size in A. montensis. For O. nigripes, hantavirusprevalence was higher in late spring, when reproduction was more frequent. Co-circulation of Juquitiba(JUQV) and Jabora (JABV) viruses was observed – JABV in A. paranaensis and A. montensis; JUQV in O.nigripes and T. nigrita. JABV occurrence was associated to gender and population size of the rodent whileJUQV was related to gender, season, temperature, and locality.