Based on tick collections recovered from wild vertebrates and by dragging, the seasonal occurrence of adult blacklegged ticks, Ixodes scapularis Say, extended from October through May: in southeastern Missouri. Adult activity was bimodal with the higher peak occurring in November followed by a lower peak in February. The activity of immature I scapularis had the general pattern of that found in the Northeast where Lyme disease is hyperendemic, with larval activity (July) peaking after that of nymphs (May and June). Vertebrates varied in their importance as hosts of I, scapularis. White-tailed deer, Odocoileus virginanus (Zimmerman ), and coyotes, Canis latrans Sag., were the primary hosts of adult I. scapularis. Broad-headed skinks, Eumeces laticeps (Schneider), and eastern fence lizards, Sceloporus undulatus (Latreille), were the primary hosts of nymphal I. scapularis. The broad-headed skink, 5-lined slink, Eumeces fasciatus (L.), and Carolina wren, Thryothorus ludovicianus (Latham), were the primary hosts of larval I, scapularis. Homeotherms were important hosts of immature I. scapularis, accounting for 30% of nymphs and 39% of larvae collected. The eastern cottontail rabbit, Sylvilagus floridanus (Allen), may play an important role in the epidemiology of Lyme disease in Missouri. Isolates of Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner were made from ticks recovered from rabbits, making the cottontail rabbit a key species for further study of the epidemiology of Lyme borreliosis in Missouri.