New organic nitrate esters, derived from structurally different (cyclo)aliphatic templates, were synthesized and pharmacologically investigated. Their in vitro vascular smooth muscle relaxing activities and, occasionally, in vivo haemodynamic profiles were studied and compared to those of the clinically important nitrates, glyceryl trinitrate, isosorbide dinitrate and isosorbide-5-mononitrate. A number of compounds appeared to be even more potent than glyceryl trinitrate. Qualitative structure-activity relationships within the series of new compounds are discussed. In flexible n-alkylene dinitrates, lipophilicity as well as chain length appears to affect in vitro activity. In semi-rigid cyclohexylene dinitrates, the number of atoms between and the configuration of the nitrate groups may play an important role. Finally, in cycloalkylene mononitrates neither the number of ring carbon atoms nor the lipophilicity clearly affects the in vitro activity. It is suggested that, apart from a limited involvement of compound lipophilicity, other factors such as differences in enzymatic conversion to a common putative bioactive species, nitric oxide, are responsible for the observed differences in activity. © 1995 Royal Dutch Association for Advancement of Pharmacy.