The volatile hydrodistilled compounds from aerial parts and rhizomes of the ethnopharmacologically highly valued plant species Geranium macrorrhizum L. were screened for their antimicrobial activity in disc-diffusion and microdilution assays. The assays pointed out to a very high and selective activity of the oils against Bacillus subtilis with minimum inhibitory concentrations (MIC) of 0.4-1.0 μg/ml. This prompted us to perform detailed compositional analyses of the oils. GC and GC/MS analyses allowed the identification of 283 constituents. The oils consisted mainly of sesquiterpenoids, the main ones being germacrone (49.7% in the oil from aerial parts) and δ-guaiene (49.2% in rhizome oil). Significant qualitative and quantitative compositional differences in the oils from the two plant parts were observed. Further antimicrobial testing enabled us to determine that germacrone, the major constituent of the oil from aerial parts, was not the sole agent responsible for the observed activity.