Amiodarone (AD)-induced pulmonary toxicity is one of the major complications of long-term AD therapy. Technetium-99m-labeled D: ,L: -hexamethylpropylene amine oxime (Tc-99m HMPAO) scintigraphy has been used to assess lung injury. We designed this study to clarify lung uptake changes of Tc-99m HMPAO using low doses of AD (5 mg/kg/day) during long-term therapy in a rabbit model. Group 1 consisted of 7 rabbits fed with AD by gavage for 6 months. To investigate the effect of ketamine on Tc-99m HMPAO uptake, 5 rabbits were included in Group 2 as a control group. Tc-99m HMPAO scintigraphy was performed in both Group 1 and Group 2 at baseline and after 2, 4, 6, 8, and 12 weeks of AD intake. After 16, 20, and 24 weeks of drug intake, Tc-99m HMPAO scintigraphy was repeated only in group 1. One-min anterior images were acquired 30 min after the injection of 37 MBq of Tc-99m HMPAO. For semiquantitative evaluation, the mean count values were obtained and lung/background and liver/background ratios were calculated. Histopathologic evaluation was performed. No increase in lung and liver uptake of Tc-99m HMPAO was found 2, 4, 6, 8, and 12 weeks after drug intake. There was no significant increase in L/B and H/B ratios of Tc-99m HMPAO in Group 1 compared with Group 2. Both scintigraphic studies and histopathologic examinations showed nonspecific changes. Longitudinal studies investigating Tc-99m HMPAO lung uptake may be planned in patients carrying risk factors for AD-induced lung toxicity.