Activated leucocytes can bind and, subsequently, phagocytose microbubbles that are used as ultrasound (US) contrast agents. The purpose of this study was to investigate whether or not microbubbles can influence the inflammatory response of human neutrophil granulocytes. Granulocytes isolated from healthy volunteers were activated with various stimuli, for example, the bacterial peptide N-formyl-methyonyl-leucyl-phenylalanine (fMLP), the calcium ionophore A23187, the protein kinase C activator phorbol myristate acetate (PMA) and the cytokine tumor necrosis factor alpha (TNF-alpha), and incubated with albumin or phospholipid microbubbles. Neutrophil respiratory burst activity and elastase release were quantified. Albumin (Optison) and phospholipid (SonoVue) contrast agents induced an extensive oxidative response of human granulocytes to all the stimuli used, and these effects could be significantly impaired by preincubation of the cells with cytochalasin B. Left heart contrast agents used for contrast-enhanced US assessment can activate human neutrophil granulocytes, inducing an extensive respiratory burst to secondary stimuli. The potential clinical relevance of this effect needs to be elucidated.