Antibiotic-resistant Burkholderia cepacia is an important pathogen in cystic fibrosis. We have previously shown enhanced tobramycin susceptibility of most strains in the presence of the drug amiloride. Others have shown similar findings in the presence of cationic agents with amine groups. To examine the relationship of substituted amine drug structure and synergy potential with tobramycin, the in vitro activity of 45 non-antibiotic substituted amine and related compounds in the presence and absence of tobramycin was studied. Very few agents had intrinsic antimicrobial action but many were very synergistic with tobramycin. Dichloroisoproterenol and propranolol were the most synergistic. Sympathomimetic, imidazoline agents, phenothiazenes, and thioxanthenes varied greatly. Exploration of these compounds may provide an avenue for treating antibiotic-resistant B. cepacia.