The external stimulus (i.e., the drug or ligand) physically binds to ("hits") the biological target. The interaction between the substance and the target may be:
* noncovalent – A relatively weak interaction between the stimulus and the target where no chemical bond is formed between the two interacting partners and hence the interaction is completely reversible.
* reversible covalent – A chemical reaction occurs between the stimulus and target in which the stimulus becomes chemically bonded to the target, but the reverse reaction also readily occurs in which the bond can be broken.
* irreversible covalent – The stimulus is permanently bound to the target through irreversible chemical bond formation.
Depending on the nature of the stimulus, the following can occur:
* There is no direct change in the biological target, but the binding of the substance prevents other endogenous substances (such as activating hormones) from binding to the target.  Depending on the nature of the target, this effect is referred as receptor antagonism, enzyme inhibition, or ion channel blockade.
* A conformational change in the target is induced by the stimulus which results in a change in target function.  This change in function can mimic the effect of the endogenous substance in which case the effect is referred to as receptor agonism (or channel or enzyme activation) or be the opposite of the endogenous substance which in the case of receptors is referred to as inverse agonism.