Two competing approaches for the roles of stimulus significance and novelty in determining orienting responses (ORs) were tested and compared. According to the first, ORs to significant stimuli are determined by sets and expectations and are relatively independent of the contrast between the test stimulus and preceding stimuli, whereas responses to nonsignificant test stimuli are products of a Sokolovian match/mismatch process. According to an alternative approach, novelty and significance contribute independently and additively to the OR. Stimulus significance and novelty were independently manipulated in two experiments, and the electrodermal component of the OR was measured while sequences comprising compound pictorial or verbal stimuli were presented. Each sequence included a test stimulus that was either significant or neutral and was preceded by several control stimuli. Novelty was manipulated by varying the contrast between the test and the control stimuli. The results revealing no interaction between stimulus significance and novelty were interpreted as supporting the theory proposed by Cati and Ben-Shakhar (1990).