diff --git a/huma.go b/huma.go
index 09aea2b2..1dc7a195 100644
--- a/huma.go
+++ b/huma.go
@@ -1379,6 +1379,13 @@ func Register[I, O any](api API, op Operation, handler func(context.Context, *I)
 			return
 		}
 
+		if output == nil {
+			// Special case: No err or output, so just set the status code and return.
+			// This is a weird case, but it's better than panicking or returning 500.
+			ctx.SetStatus(op.DefaultStatus)
+			return
+		}
+
 		// Serialize output headers
 		ct := ""
 		vo := reflect.ValueOf(output).Elem()
diff --git a/huma_test.go b/huma_test.go
index 3856dad8..9c24812d 100644
--- a/huma_test.go
+++ b/huma_test.go
@@ -1432,6 +1432,30 @@ Content of example2.txt.
 				assert.JSONEq(t, `{"$schema": "https:///schemas/RespBody.json", "greeting":"Hello, world!"}`, resp.Body.String())
 			},
 		},
+		{
+			Name: "response-nil",
+			Register: func(t *testing.T, api huma.API) {
+				type Resp struct {
+					Body struct {
+						Greeting string `json:"greeting"`
+					}
+				}
+
+				huma.Register(api, huma.Operation{
+					Method: http.MethodGet,
+					Path:   "/response",
+				}, func(ctx context.Context, input *struct{}) (*Resp, error) {
+					return nil, nil
+				})
+			},
+			Method: http.MethodGet,
+			URL:    "/response",
+			Assert: func(t *testing.T, resp *httptest.ResponseRecorder) {
+				// This should not panic and should return the default status code,
+				// which for responses which normally have a body is 200.
+				assert.Equal(t, http.StatusOK, resp.Code)
+			},
+		},
 		{
 			Name: "response-raw",
 			Register: func(t *testing.T, api huma.API) {