A case-control study to identify risk factors for fracture of the shafts of the tibia and fibula among persons 45 years of age and older was undertaken in five Northern California Kaiser Permanente Medical Centers during 1996-2001. One hundred seventy-nine cases of newly diagnosed fracture of the tibia/fibula shaft and 2,399 controls sampled from the membership lists of the same five medical centers were included. Information on potential risk factors was obtained by a standardized questionnaire administered by trained interviewers. The number of previous fractures was associated with an increased risk [adjusted odds ratio (OR) (95% confidence interval)=1.49 (1.09-2.03) per previous fracture]. Attributes known or thought to be associated with protection against loss of bone mass, including high body mass index [adjusted OR=0.82 (0.69-0.97) per 5 kg/m2 increase], having ever used thiazide diuretics or water pills for at least 1 year [adjusted OR=0.62 (0.38-1.02)], and current use of menopausal hormone therapy among females [adjusted OR=0.84 (0.53-1.32)] tended to show decreased risks. Factors generally associated with lower bone mass, such as current cigarette smoking [OR=1.55 (1.01-2.39)] and, to some extent, lack of physical activity [OR=1.31 (0.87-1.96) for the lowest quartile compared to the upper three quartiles], tended to demonstrate increased risks. The number of falls in the past year and risk factors for falls were not associated with tibia/fibula shaft fractures, and indicators of health status were weakly and inconsistently associated with risk. Thus, this study suggests that risk factors for low bone mass, but not health status or risk factors for falls, may be important in the etiology of fracture of the shaft of the tibia/fibula in older individuals.