Abstract: Comparative studies on the antimicrobial activities and phytochemical screening of two varieties of Acalypha wilkesiana were carried to investigate the inhibitory potential on some selected pathogens and determine the phytoconstituents of pharmacologic importance. Ethanol was used as the extraction solvent and the microorganisms used were Staphylococcus aureus, S. epidermidis Clostridium sporogenes, B. cereus, B. subtilis, Klebsiella pneunoniae, Trichophyton interdistale, Aspergillus niger, Penicillium camenberti and Fusarium solanni. Growth inhibition indicates on agar plate was used for the antimicrobial sensitivity. The extract was found to posses� broad spectrum of activity on both fungi and the bacteria; the latter found was to be more susceptible. Generally Macrophylla variety was found to be more effective in inhibiting the growth of the organisms than Hoffmanin. The Gram- negative organisms like Klebsiella and Pseudomonas was found to be more resistance than the Gram-positive organism as indicated by zone of inhibition. The release of sodium and potassium ions was found to be the mechanism of action of the extract and the amount leaked vary from one organism to the other and is also dependent on the Acalypha variety. Minimum inhibitory concentration (MIC) vary between 0.2-0.98. Comparing the efficacy of the extract with commercial antibiotics showed that the latter was more potent but with narrow spectrum of activity only on the fungi unlike the former with broad spectrum of activity on both fungi and bacteria. The bioactive compounds in the extract include saponin, Tannin, Anthroquinine and glycoside.