Objective: As part of the innate immune system leucocytes play a major role in the inflammatory response. Neutrophil granulocytes circulate in the blood vessel system until they are activated and recruited into inflamed tissues. Attracted by cytokines they transmigrate the endothelium and migrate into affected tissue. During chemotaxis cells become morphologically polarised which means that the gradient of the chemoattractant is transduced into protrusion at the front and retraction of the rear part of the cell. This signal transduction utilizes Ca²⁺ transients. On our way to identify the involved Ca²⁺ entry channels we investigated the role of TRPC1 and TRPC6, members of the transient receptor potential (TRP) channel family. Methods: We studied the impact of either TRPC1 or TRPC6 knockout on migration of murine neutrophils in 2- and 3-dimensional matrices with time-lapse videomicroscopy. We used the bacterial N-formylated peptide fMLP (formyl-methionyl-leucyl-phenylalanine) or a chemokine cocktail in chemotaxis essays. Results: Chemotaxis of TRPC6-/- neutrophils along a chemokine cocktail gradient was decreased. Furthermore migration velocity and translocation were reduced in TRPC6-/- cells. However, chemotaxis towards fMLP was not affected in TRPC6-/- neutrophils. In contrast, deletion of TRPC1 reduced velocity, translocation and chemotaxis of fMLP stimulated cells. Conclusion: Our findings indicate that both TRPC1 and TRPC6 may be involved in chemotactic signaling of murine neutrophils.