The allylamine class of antifungal compounds are specific inhibitors of squalene epoxidase (SE). However, depending on their chemical structure, allylamine derivatives can be highly selective for either fungal or mammalian SEs. All allylamines tested previously, irrespective of their selectivity, inhibit fungal SEs in a noncompetitive manner and mammalian SEs in a competitive manner. Here we have analyzed the inhibitory properties of the benzylamine SDZ SBA 586 toward fungal and mammalian SEs in comparison to the systemic antimycotic terbinafine, SDZ SBA 586 was, like terbinafine a selective inhibitor of fungal SE. Microsomal SE from the pathogenic yeast candida albicans was sixfold more sensitive to SDZ SBA 586 than to terbinafine, C50: 8 nM versus 44 nM, while the enzyme from the dermatophyte fungus Trichophyton rubrum was slightly less sensitive to SDZ SBA 586 than to terbinafine, IC50: 39 and 18 nM, respectively. Similarly to terbinafine, SDZ SBA 586 inhibited the yeast enzyme in non competitive manner, SDZ SBA 586 also inhibited mammalian microsomal SEs, but only at micromolar concentrations. It was more active than terbinafine toward both guinea pig SE, IC50: 2 microM versus 4 microM, and rat SE, IC50: 11 microM versus 87 microM. However, in contrast to terbinafine as well as allylamines selective for mammalian SE, SDZ SBA 586 was a noncompetitive inhibitor of rat microsomal SE. Interestingly, depending on the source of microsomal SE, binding of terbinafine and SDZ SBA 586 exhibited a positive, indifferent, or negative cooperativity, suggesting that SE is an oligomeric enzyme.