Canine heartworm disease is caused by infection with Dirofilaria immitis, a filarial nematode that resides in the pulmonary arteries and occasionally in the right heart chambers of infected dogs. Here the authors evaluated the effect of a combination of doxycycline (10 mg/kg/sid for 30 days) and ivermectin–pyrantel(6g/kg of ivermectin+5mg/kg of pyrantel every 15 days for 180 days) on microfilariemia, antigenemia and parasite load at echocardiography in naturally infected dogs from an endemic region of Italy [corrected]. Dogs were examined monthly for 6 months and followed-up 4 months later. One hundred percent of dogs became negative for circulating microfilariae by day 90, while 8/11 (72.7%) of dogs became antigen-negative by day 300. Of the 7 dogs that were positive for visualization of parasites at echocardiography, 6 (85.7%) became negative by day 300. Treatment was well-tolerated by all dogs. These results suggest that a combination of doxycycline and ivermectin is adulticide in dogs with D. immitis.